CyclinG contributes to G2/M arrest of cells in response to DNA damage.
To investigate regulation mechanisms of G2/M phase transition, we studied the association of cell cycle progression with p53-dependent p21/waf-1 and cyclinG expression. We used doxorubicin (DOX) and sodium butyrate (NaB) to accumulate p53 protein. DOX treatment resulted in an apparent increase of cells in the G2/M fraction, whereas NaB arrested cells at G1. P53 protein induction in response to DOX accompanied up-regulation of p21/waf-1 and cyclinG expression. However, cyclinG was undetectable in NaB-treated cells. These results implied a putative association between increases in the proportion of cells accumulating in the G2/M fraction and enhanced cyclinG expression. Antisense oligo DNAs (AS) complementary to cyclinG mRNA inhibited the cyclinG protein expression induced by DOX treatment. This inhibition resulted in a marked reduction in the number of cells arrested at G2/M and accumulating at G1. A role for cyclinG in G2/M phase transition control is implied.
Shimizu
A
A
Department of Reproductive Physiolosy and Endocrinology, Kyushu University, Oita, Japan.
Nishida
J
J
Ueoka
Y
Y
Kato
K
K
Hachiya
T
T
Kuriaki
Y
Y
Wake
N
N
D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002453:Cell Cycle / Q000187:drug effects*; D056746:Cyclin G; D056766:Cyclin G1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics*; D016373:DNA, Antisense / Q000235:genetics / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts; D016195:G2 Phase / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D015151:Immunoblotting; D008938:Mitosis / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D002087:Butyrates; C534704:Ccng1 protein, rat; C493958:Cdkn1a protein, rat; D056746:Cyclin G; D056766:Cyclin G1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016373:DNA, Antisense; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D020148:Butyric Acid; D004317:Doxorubicin